EU approves Novartis's 'mock-up' pandemic vaccine

May 9, 2007 (CIDRAP News) – The European Union (EU) this week approved a "mock-up" influenza vaccine made by Novartis to permit a faster start on vaccine production in the event of a flu pandemic.

When the World Health Organization (WHO) declares a flu pandemic, the vaccine, called Focetria, will be adapted to contain the pandemic virus, the Swiss-based drug company announced yesterday. The vaccine will not be manufactured until a pandemic is declared.

The European Medicines Agency's (EMEA's) Committee for Medicinal Products for Human Use (CHMP) recommended approval of Focetria on Feb 22. A CHMP statement on that date said the vaccine was based on a 2004 strain of H5N1 avian flu from Vietnam.

The vaccine contains Novartis's proprietary adjuvant MF59, an immune-boosting chemical, which can reduce the amount of active ingredient needed in each dose, the company says. The dose used in the approved mock-up vaccine is 15 micrograms (mcg), according to the CHMP.

"Once the WHO declares a pandemic, Novartis will submit a revised application to the European Medicines Agency to incorporate the identified viral strain," Novartis officials said in a news release yesterday. "The Focetria mock-up file submitted for EU approval in early 2006 was based on clinical studies involving the MF59 adjuvant and different influenza strains with pandemic potential, including H5N1 and H9N2."

A CHMP statement from December 2006 defines a mock-up vaccine as one "that mimics the future pandemic influenza vaccine in terms of its composition and manufacturing method" but contains a different flu strain.

Novartis said it is also seeking EU approval for a prepandemic H5N1 vaccine that includes MF59 and is based on the same technology as Focetria. The vaccine is intended for use before a pandemic declaration to help "prime" the immune system to fight off H5N1 infections, the company says.

Both Focetria and the prepandemic vaccine involve the conventional production method of growing the vaccine virus in eggs, according to Eric Althoff, a Novartis spokesman in Emeryville, Calif.

Once a pandemic flu strain is identified, it will take at least 6 months to adapt the virus for production in eggs and start producing the vaccine in quantity, Althoff told CIDRAP News yesterday.

"It'll be at least 6 months, just from the simple time of getting enough raw material, ie, eggs, to have full-scale production," he said.

On Apr 26 the CHMP recommended EU approval of a Novartis seasonal flu vaccine grown in cell culture instead of in eggs. Althoff said the company also aims to make a cell culture–based pandemic flu vaccine, but development is in an early stage.

Cell-culture production is described as somewhat faster and much more flexible than egg-based production. No cell-based flu vaccine has been marketed anywhere as yet, though the EU in 2001 approved a cell-based seasonal flu vaccine made by Solvay Pharmaceuticals for sale in the Netherlands.

Althoff said Novartis is talking with US regulators about how to seek approval for both pandemic mock-up and prepandemic vaccines. European authorities provided guidance earlier than the US Food and Drug Administration (FDA) did on the steps needed to get approval for a mock-up vaccine, he said.

"That pathway hadn't been mapped out by the FDA or how to handle the review and approval of such a vaccine," he said. But an FDA advisory committee recently prescribed the necessary steps, he added. "I think there's great progress now and more clarity about how to move forward."

In April the FDA approved an H5N1 vaccine made by Sanofi Pasteur, despite only modest immunogenicity demonstrated in clinical trials. The Department of Health and Human Services has been stockpiling the vaccine for use in a pandemic.